ADAMTS3 (ADAM metallopeptidase with thrombospondin type 1 motif 3)

Gene

• Entrez ID: 9508
• Gene name: ADAM metallopeptidase with thrombospondin type 1 motif 3
• Gene symbol: ADAMTS3
• Synonyms (NCBI Gene): ADAMTS-4, HKLLS3
• Chromosome: 4
• Chromosome location: 4q13.3
• Summary: This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegri

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs61757480	A>G	Pathogenic	Missense variant, coding sequence variant
rs747975445	G>A,T	Pathogenic	Synonymous variant, coding sequence variant, stop gained
rs1177851177	A>G	Pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT766617	hsa-miR-147	CLIP-seq
MIRT766618	hsa-miR-185	CLIP-seq
MIRT766619	hsa-miR-2054	CLIP-seq
MIRT766620	hsa-miR-219-1-3p	CLIP-seq
MIRT766621	hsa-miR-30a	CLIP-seq
MIRT766622	hsa-miR-30b	CLIP-seq
MIRT766623	hsa-miR-30c	CLIP-seq
MIRT766624	hsa-miR-30d	CLIP-seq
MIRT766625	hsa-miR-30e	CLIP-seq
MIRT766626	hsa-miR-3140-3p	CLIP-seq
MIRT766627	hsa-miR-3149	CLIP-seq
MIRT766628	hsa-miR-3171	CLIP-seq
MIRT766629	hsa-miR-3688-3p	CLIP-seq
MIRT766630	hsa-miR-380	CLIP-seq
MIRT766631	hsa-miR-411	CLIP-seq
MIRT766632	hsa-miR-4254	CLIP-seq
MIRT766633	hsa-miR-4261	CLIP-seq
MIRT766634	hsa-miR-4292	CLIP-seq
MIRT766635	hsa-miR-4306	CLIP-seq
MIRT766636	hsa-miR-4308	CLIP-seq
MIRT766637	hsa-miR-4328	CLIP-seq
MIRT766638	hsa-miR-452	CLIP-seq
MIRT766639	hsa-miR-4644	CLIP-seq
MIRT766640	hsa-miR-4676-3p	CLIP-seq
MIRT766641	hsa-miR-4715-5p	CLIP-seq
MIRT766642	hsa-miR-4731-3p	CLIP-seq
MIRT766643	hsa-miR-4738-3p	CLIP-seq
MIRT766644	hsa-miR-4801	CLIP-seq
MIRT766645	hsa-miR-501-3p	CLIP-seq
MIRT766646	hsa-miR-502-3p	CLIP-seq
MIRT766647	hsa-miR-505	CLIP-seq
MIRT766648	hsa-miR-548g	CLIP-seq
MIRT766649	hsa-miR-571	CLIP-seq
MIRT766650	hsa-miR-591	CLIP-seq
MIRT766651	hsa-miR-599	CLIP-seq
MIRT766652	hsa-miR-647	CLIP-seq
MIRT766629	hsa-miR-3688-3p	CLIP-seq
MIRT766619	hsa-miR-2054	CLIP-seq
MIRT766638	hsa-miR-452	CLIP-seq
MIRT766640	hsa-miR-4676-3p	CLIP-seq
MIRT766617	hsa-miR-147	CLIP-seq
MIRT2167220	hsa-miR-202	CLIP-seq
MIRT766629	hsa-miR-3688-3p	CLIP-seq
MIRT766633	hsa-miR-4261	CLIP-seq
MIRT766638	hsa-miR-452	CLIP-seq
MIRT766640	hsa-miR-4676-3p	CLIP-seq
MIRT766643	hsa-miR-4738-3p	CLIP-seq
MIRT766648	hsa-miR-548g	CLIP-seq
MIRT766651	hsa-miR-599	CLIP-seq
MIRT2167221	hsa-miR-875-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001701	Process	In utero embryonic development	IEA
GO:0004175	Function	Endopeptidase activity	IDA	24552833
GO:0004222	Function	Metalloendopeptidase activity	IBA
GO:0004222	Function	Metalloendopeptidase activity	IEA
GO:0004222	Function	Metalloendopeptidase activity	NAS	11812023
GO:0004222	Function	Metalloendopeptidase activity	TAS
GO:0005515	Function	Protein binding	IPI	24552833, 32296183
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IDA	24552833
GO:0006508	Process	Proteolysis	IBA
GO:0006508	Process	Proteolysis	IEA
GO:0008201	Function	Heparin binding	IEA
GO:0008233	Function	Peptidase activity	IEA
GO:0008237	Function	Metallopeptidase activity	IEA
GO:0008270	Function	Zinc ion binding	NAS	11408482
GO:0010573	Process	Vascular endothelial growth factor production	IDA	24552833
GO:0016485	Process	Protein processing	IDA	11408482, 24552833
GO:0016485	Process	Protein processing	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0030198	Process	Extracellular matrix organization	IBA
GO:0030198	Process	Extracellular matrix organization	IEA
GO:0030199	Process	Collagen fibril organization	IC	11408482
GO:0030199	Process	Collagen fibril organization	IEA
GO:0030199	Process	Collagen fibril organization	NAS	11812023
GO:0030199	Process	Collagen fibril organization	TAS
GO:0030574	Process	Collagen catabolic process	NAS	11408482
GO:0031012	Component	Extracellular matrix	IBA
GO:0031012	Component	Extracellular matrix	NAS	11812023
GO:0031012	Component	Extracellular matrix	TAS	22261194
GO:0032964	Process	Collagen biosynthetic process	IDA	11408482
GO:0046872	Function	Metal ion binding	IEA
GO:0070062	Component	Extracellular exosome	HDA	19199708
GO:0097435	Process	Supramolecular fiber organization	IC	11408482
GO:1900748	Process	Positive regulation of vascular endothelial growth factor signaling pathway	IDA	24552833

Other IDs

• MIM: 605011
• HGNC: 219
• e!Ensembl: ENSG00000156140

Protein

• UniProt ID: O15072
• Protein name: A disintegrin and metalloproteinase with thrombospondin motifs 3 (ADAM-TS 3) (ADAM-TS3) (ADAMTS-3) (EC 3.4.24.-) (Procollagen II N-proteinase) (PC II-NP) (Procollagen II amino propeptide-processing enzyme)
• Protein function: Cleaves the propeptides of type II collagen prior to fibril assembly. Does not act on types I and III collagens.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01562	Pep_M12B_propep	43 → 201	Reprolysin family propeptide	Family
  PF01421	Reprolysin	257 → 460	Reprolysin (M12B) family zinc metalloprotease	Domain
  PF17771	ADAM_CR_2	472 → 541	ADAM cysteine-rich domain	Domain
  PF00090	TSP_1	553 → 605	Thrombospondin type 1 domain	Domain
  PF05986	ADAM_spacer1	713 → 827	ADAM-TS Spacer 1	Family
  PF19030	TSP1_ADAMTS	849 → 904		Domain
  PF19030	TSP1_ADAMTS	909 → 966		Domain
  PF19030	TSP1_ADAMTS	970 → 1015		Domain

• Tissue specificity: TISSUE SPECIFICITY: Found in cartilage and skin.
• Sequence:

  MVLLSLWLIAAALVEVRTSADGQAGNEEMVQIDLPIKRYREYELVTPVSTNLEGRYLSHT
  LSASHKKRSARDVSSNPEQLFFNITAFGKDFHLRLKPNTQLVAPGAVVEWHETSLVPGNI
  TDPINNHQPGSATYRIRRTEPLQTNCAYVGDIVDIPGTSVAISNCDGLAGMIKSDNEEYF
  IEPLERGKQMEEEKGRIHVVYKRSAVEQAPIDMSKDFHYRESDLEGLDDLGTVYGNIHQQ
  LNETMRRRRHAGENDYNIEVLLGVDDSVVRFHGKEHVQNYLLTLMNIVNEIYHDESLGVH
  INVVLVRMIMLGYAKSISLIERGNPSRSLENVCRWASQQQRSDLNHSEHHDHAIFLTRQD
  FGPAGMQGYAPVTGMCHPVRSCTLNHEDGFSSAFVVAHETGHVLGMEHDGQGNRCGDETA
  MGSVMAPLVQAAFHRYHWSRCSGQELKRYIHSYDCLLDDPFDHDWPKLPELPGINYSMDE
  QCRFDFGVGYKMCTAFRTFDPCKQLWCSHPDNPYFCKTKKGPPLDGTECAAGKWCYKGHC
  MWKNANQQKQDGNWGSWTKFGSCSRTCGTGVRFRTRQCNNPMPINGGQDCPGVNFEYQLC
  NTEECQKHFEDFRAQQCQQRNSHFEYQNTKHHWLPYEHPDPKKRCHLYCQSKETGDVAYM
  KQLVHDGTHCSYKDPYSICVRGECVKVGCDKEIGSNKVEDKCGVCGGDNSHCRTVKGTFT
  RTPRKLGYLKMFDIPPGARHVLIQEDEASPHILAIKNQATGHYILNGKGEEAKSRTFIDL
  GVEWDYNIEDDIESLHTDGPLHDPVIVLIIPQENDTRSSLTYKYIIHEDSVPTINSNNVI
  QEELDTFEWALKSWSQCSKPCGGGFQYTKYGCRRKSDNKMVHRSFCEANKKPKPIRRMCN
  IQECTHPLWVAEEWEHCTKTCGSSGYQLRTVRCLQPLLDGTNRSVHSKYCMGDRPESRRP
  CNRVPCPAQWKTGPWSECSVTCGEGTEVRQVLCRAGDHCDGEKPESVRACQLPPCNDEPC
  LGDKSIFCQMEVLARYCSIPGYNKLCCESCSKRSSTLPPPYLLEAAETHDDVISNPSDLP
  RSLVMPTSLVPYHSETPAKKMSLSSISSVGGPNAYAAFRPNSKPDGANLRQRSAQQAGSK
  TVRLVTVPSSPPTKRVHLSSASQMAAASFFAASDSIGASSQARTSKKDGKIIDNRRPTRS
  STLER

• Sequence length: 1205

Pathways

Reactome:

Collagen biosynthesis and modifying enzymes
Defective B3GALTL causes Peters-plus syndrome (PpS)
O-glycosylation of TSR domain-containing proteins

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Hennekam lymphangiectasia-lymphedema syndrome 3	Pathogenic	rs1177851177, rs61757480, rs747975445	RCV000714297 RCV000714298 RCV000770924	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ADAMTS3-related disorder	Benign; Likely benign; Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ARTERY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DENTAL CARIES	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HENNEKAM LYMPHANGIECTASIA-LYMPHEDEMA SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HENNEKAM SYNDROME	—	GWAS catalog, Orphanet GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prostate cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Amyotrophic Lateral Sclerosis	Amyotrophic Lateral Sclerosis	BEFREE	28084617		★☆☆☆☆ Found in Text Mining only
Aortic Rupture	Aortic Rupture	BEFREE	28955046		★☆☆☆☆ Found in Text Mining only
Arteriosclerosis	Arteriosclerosis	BEFREE	20652528, 21334453		★☆☆☆☆ Found in Text Mining only
Arthritis	Arthritis	BEFREE	28084617		★☆☆☆☆ Found in Text Mining only
Arthritis, Gouty	Gouty arthritis	BEFREE	26637956		★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	BEFREE	20652528, 21334453		★☆☆☆☆ Found in Text Mining only
Benign neoplasm of central nervous system	Benign Neoplasm Of Nervous System	HPO_DG			★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	28099917		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	25261644	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	36514188	Associate	★☆☆☆☆ Found in Text Mining only
Chondrosarcoma	Chondrosarcoma	BEFREE	11408482		★☆☆☆☆ Found in Text Mining only
Chondrosarcoma	Chondrosarcoma	Pubtator	11408482	Associate	★☆☆☆☆ Found in Text Mining only
CNS disorder	CNS Disorder	BEFREE	28084617		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	25786261, 29694979		★☆☆☆☆ Found in Text Mining only
Conductive hearing loss	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cone-Rod Dystrophy 2	Cone-rod dystrophy	BEFREE	28084617		★☆☆☆☆ Found in Text Mining only
Congenital arteriovenous malformation	Congenital Arteriovenous Malformation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Epicanthus	Congenital Epicanthus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Craniosynostosis	Craniosynostosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	BEFREE	15708897, 16200590, 18941754, 19684582, 20652528, 23897278, 23965695, 25501175, 26818776, 27082728, 28216310, 28237856, 28256567, 29236314, 29393494, 30210670, 30700002, 31463904		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Insulin-Dependent	Diabetes Mellitus	BEFREE	25299465		★☆☆☆☆ Found in Text Mining only
Ectopic kidney	Ectopic kidney	HPO_DG			★☆☆☆☆ Found in Text Mining only
EHLERS-DANLOS SYNDROME, DERMATOSPARAXIS TYPE	Dermatosparaxis Ehlers-Danlos Syndrome	BEFREE	11408482		★☆☆☆☆ Found in Text Mining only
Erysipelas	Erysipelas	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glaucoma	Glaucoma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	36514188	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	36514188	Associate	★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	32299451	Associate	★☆☆☆☆ Found in Text Mining only
Heart Defects Congenital	Congenital heart defect	Pubtator	32299451	Associate	★☆☆☆☆ Found in Text Mining only
Hennekam lymphangiectasia lymphedema syndrome	Hennekam syndrome	Pubtator	28985353, 37322437	Associate	★☆☆☆☆ Found in Text Mining only
Hennekam lymphangiectasia-lymphedema syndrome	Hennekam lymphangiectasia-lymphedema syndrome	ORPHANET_DG	28985353		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hennekam lymphangiectasia-lymphedema syndrome	Hennekam lymphangiectasia-lymphedema syndrome	BEFREE	30450763		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HENNEKAM LYMPHANGIECTASIA-LYMPHEDEMA SYNDROME 3	Hennekam lymphangiectasia-lymphedema syndrome	BEFREE	28985353		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
HENNEKAM LYMPHANGIECTASIA-LYMPHEDEMA SYNDROME 3	Hennekam lymphangiectasia-lymphedema syndrome	UNIPROT_DG	28985353		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
HENNEKAM LYMPHANGIECTASIA-LYMPHEDEMA SYNDROME 3	Hennekam lymphangiectasia-lymphedema syndrome	GENOMICS_ENGLAND_DG	30450763		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
HENNEKAM LYMPHANGIECTASIA-LYMPHEDEMA SYNDROME 3	Hennekam lymphangiectasia-lymphedema syndrome	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hennekam syndrome	Hennekam Syndrome	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Horseshoe Kidney	Horseshoe Kidney	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hydrops Fetalis	Hydrops Fetalis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	32299451	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intervertebral Disc Degeneration	Intervertebral Disc Degeneration	BEFREE	16741450, 23778376, 28512264, 31251999		★☆☆☆☆ Found in Text Mining only
Intervertebral disc disorder	Intervertebral Disc Disorder	BEFREE	25299465		★☆☆☆☆ Found in Text Mining only
Intervertebral Disk Displacement	Intervertebral Disk Displacement	BEFREE	16741450		★☆☆☆☆ Found in Text Mining only
Ischemic stroke	Ischemic Stroke	BEFREE	28084617		★☆☆☆☆ Found in Text Mining only
Keratoconus	Keratoconus	Pubtator	32867823	Associate	★☆☆☆☆ Found in Text Mining only
Laryngeal Squamous Cell Carcinoma	Laryngeal Carcinoma	BEFREE	23131589		★☆☆☆☆ Found in Text Mining only
Lhermitte-Duclos disease	Lhermitte-Duclos disease	BEFREE	26495885		★☆☆☆☆ Found in Text Mining only
Lumbar disc disease	Lumbar Disc Disease	BEFREE	26495885		★☆☆☆☆ Found in Text Mining only
Lymphangioma	Lymphangioma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lymphedema	Lymphedema	Pubtator	28985353, 37322437	Associate	★☆☆☆☆ Found in Text Mining only
Lymphopenia	Lymphopenia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malabsorption Syndrome	Malabsorption Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	28099917		★☆☆☆☆ Found in Text Mining only
Melanoma Cutaneous Malignant	Melanoma	Pubtator	28796414	Associate	★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic syndrome	Pubtator	29084231	Associate	★☆☆☆☆ Found in Text Mining only
Microstomia	Microstomia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple Sclerosis	BEFREE	16900752		★☆☆☆☆ Found in Text Mining only
Osteoarthritis	Osteoarthritis	Pubtator	15708897	Associate	★☆☆☆☆ Found in Text Mining only
Osteoarthritis of hip	Osteoarthritis Of Hip	BEFREE	15708897, 26791034		★☆☆☆☆ Found in Text Mining only
Osteoarthritis, Knee	Knee osteoarthritis	BEFREE	25501175		★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	BEFREE	24752352, 29518549		★☆☆☆☆ Found in Text Mining only
Pachygyria	Pachygyria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pericardial effusion	Pericardial effusion	HPO_DG			★☆☆☆☆ Found in Text Mining only
Protein-Losing Enteropathies	Protein-losing enteropathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Rheumatoid Arthritis	Rheumatoid arthritis	BEFREE	22324945, 25707877		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	CTD_human_DG	21822266		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sleep Apnea Syndromes	Sleep Apnea	BEFREE	31420786		★☆☆☆☆ Found in Text Mining only
Sleep Apnea, Obstructive	Sleep Apnea	BEFREE	31420786		★☆☆☆☆ Found in Text Mining only
Syndactyly of fingers	Syndactyly of fingers	HPO_DG			★☆☆☆☆ Found in Text Mining only
Tendinopathy	Tendinopathy	BEFREE	18387286		★☆☆☆☆ Found in Text Mining only
Testicular Hydrocele	Testicular Hydrocele	HPO_DG			★☆☆☆☆ Found in Text Mining only